Venous thromboembolic disease (VTED) remains a major natural health hazard. Use of the proven prophylactic agents for prevention of postoperative VTED has not been well accepted. Safer, simpler and more economic modes of prophylaxis are needed. Data from Harris et al (8,15) Zeckert (17) and McKenna et al (18) support the efficacy and safety of aspirin as a prophylactic agent following total hip replacement (THR), hip fractures and total knee replacement (TKR). This conclusion is challenged by Stamatakis et al (19). Moreover, the question of optimum dose is unresolved. While substantial evidence would indicate that low doses would be preferable (20-23) because of the differential sensitivity to aspirin of thromboxane synthesis in platelets versus that of the endothelial synthesis of prostacyclin, McKenna et al (18) found that 3900 mg was effective following TKR but 900 mg daily was not. McKenna et al and Zeckert did not find a sex preference in the prophylaxis while Harris et al found protection only for men. Resolution of these conflicts is of major importance. Equally so is a critical evaluation of the possibility of protection in hip patients using external pneumatic compression (EPC). We propose a bicentric study with Prof. Jack Hirsh's group at McMaster University, investigating the safety and efficacy of four regimes in patients over 40 years of age undergoing THR. The studies at McMaster will be identical to those at the M.G.H., except for differences in one prophylactic group at each institution. Funding for the McMaster study will be entirely separate from this grant. Patients will be grouped by sex, age, and known prior VTED. All diagnoses will be by venography or V/Q scans plus pulmonary angiography is required. The three prophylactic regimes at the M.G.H. will be 0.6 gm aspirin b.i.d., 0.50 gm aspirin b.i.d., and the combination of low molecular weight dextran with EPC. At McMaster the three regimes will be 0.6 grams aspirin b.i.d., dextran alone, and dextran plus EPC.